Relapse of hematologic malignancy is a major problem in allogeneic bone marrow transplantation (BMT). There is circumstantial evidence for the existence of a graft-versus-leukemia (GVL) effect exerted by cells from the donor marrow. It is postulated that Interleukin-2 (IL-2) may induce or amplify a GVL effect by activating appropriate donor T cells, by inducing secretion of other cytokines, and/or by activating non-specific effectors such as lymphokine-activated killer (LAK) cells. In humans, IL-2, alone or in combination with ex vivo-generated LAK cells, has induced remissions of some cancers, including lymphomas and acute leukemias. Moreover, IL-2/LAK therapy is not cross-resistant with chemoradiotherapy and should be most effective in a setting of minimal residual disease, such as exists early after BMT. The GVL effect has been documented only in recipients of unmodified allogeneic marrow-especially those with graft-versus-host disease (GVHD). Therefore, recipients of unmodified marrow, especially those without GVHD, who are at high risk for relapse, are appropriate subjects for attempts to amplify a GVL effect by stimulating T and/or non-T effector mechanisms. Recipients of T depleted marrow who are at low risk for GVHD but at high risk for relapse, are also appropriate subjects for attempts to induce a GVL effect since cells which acquire LAK activity on exposure to IL-2 in vitro are detectable in their blood very early after BMT. Accordingly, the specific aims of this project are as follows: (1) to assess the toxicity and immunomodulatory effects of IL-2 in a Phase Ib trial for patients who have received unmodified HLA-matched sibling marrow for hematologic malignancy, (2) based on data anticipated from 1, to design and perform a Phase II trial of a combination of IL-2 and ex vivo generated LAK cells to decrease the relapse rate in patients who have undergone HLA- matched sibling BMT and who are at high risk for leukemia relapse, (3) to assess the toxicity and immunomodulatory effects of IL-2 via a Phase Ib trial in patients who have undergone a T-depleted second HLA-matched allogeneic BMT for recurrent disease; and (4) based on data anticipated from 3, to design and perform a Phase II trial of a combination of IL-2 and ex vivo generated LAK cells to decrease the relapse rate in patients who have undergone T-depleted second HLA identical BMT for recurrent disease. The results should enhance our understanding of the GVL effect in BMT and might lead to an effective new treatment modality in the context of BMT for hematologic malignancies.